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| ID | Type | Description | Link |
|---|---|---|---|
| U54NS065768 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Rare Diseases Clinical Research Network | NETWORK |
| National Center for Advancing Translational Sciences (NCATS) | NIH |
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
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The investigators are interested in determining if the investigators are able to detect changes in brain chemistry using Magnetic Resonance Spectroscopy (MRS) in individuals with Parkinson's disease (PD), those with Gaucher's disease (GD), and those without neurological disorders (healthy controls) when they are given the antioxidant N-acetylcysteine (NAC). This study will combine information from a medical history, a physical examination and disease rating scales with results obtained using MRS brain scans and pharmacokinetic studies from blood samples. This research will require 1 visit that will require about 4 to 5 hours of time. During this study, participants will provide their medical history, be examined and undergo a rating scale for about one hour; the brain scan and pharmacokinetic studies will require 1.5-2 hours of time; in total the study will take about 4-5 hours.
Oxidative stress is implicated in the pathogenesis of a number of neurodegenerative diseases such as Parkinson's disease (PD). Further, levels of glutathione (GSH), a prevalent endogenous antioxidant, are decreased in the postmortem substantia nigra (SN) of individuals with PD, indicating increased oxidative stress, although this has yet not been confirmed in vivo. Increases in intracellular oxidative stress have also been observed in primary fibroblast cultures obtained from patients with GD, where enzyme replacement therapy resulted in increases in total GSH. The hypothesis that oxidative stress plays a key role in the neurodegeneration associated with PD suggests that antioxidants may be useful in altering disease progression.
N-acetylcysteine (NAC) is a well-known antioxidant that is thought to act both as a free radical scavenger and as a cysteine donor for the synthesis of GSH. NAC may be beneficial in the treatment of PD and GD. Magnetic resonance spectroscopy (MRS) methods may be able to determine if there are effects from NAC on central nervous system GSH levels. In addition, use of red blood cell (RBC) measurements of GSH, if correlated with brain concentrations, could serve as an easily measured biomarker to help characterize and monitor response to therapy. The investigators therefore propose to conduct a study of the effect of a single, intravenous dose of NAC on central (brain) measures of GSH and peripheral (RBC) measures of GSH in people with PD and healthy controls, through the use of simultaneous MRS techniques and pharmacokinetic studies. The investigators hypothesis and specific aims are as follows:
Hypothesis: RBC and brain GSH concentrations will increase following oral NAC administration in individuals with Parkinson's disease (PD), Gaucher's disease (GD), and control participants.
Specific Aims:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NAC in PD | Experimental | single intravenous administration of N-acetylcysteine in PD patients |
|
| NAC in GD | Experimental | single intravenous administration of N-acetylcysteine in GD patients |
|
| NAC in controls | Experimental | single intravenous administration of N-acetylcysteine in control subjects |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| N-acetylcysteine | Drug | Single, intravenous administration of N-acetylcysteine |
|
| Measure | Description | Time Frame |
|---|---|---|
| Brain GSH | change in brain GSH levels from baseline to post-NAC administration (90 - 110 minutes) in all subjects | Baseline and up to 110 minutes post-NAC administration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Paul Tuite, MD | University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23860343 | Derived | Holmay MJ, Terpstra M, Coles LD, Mishra U, Ahlskog M, Oz G, Cloyd JC, Tuite PJ. N-Acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson diseases. Clin Neuropharmacol. 2013 Jul-Aug;36(4):103-6. doi: 10.1097/WNF.0b013e31829ae713. |
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Groups were not assigned in this study. All subjects received the same intervention.
Subjects were primarily recruited from the investigators' clinics at the University of Minnesota, and from research volunteers signed up with the University's Center for Magnetic Resonance Research.
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| ID | Title | Description |
|---|---|---|
| FG000 | NAC in PD | single intravenous administration of N-acetylcysteine in PD patients |
| FG001 | NAC in GD | single intravenous administration of N-acetylcysteine in GD patients |
| FG002 | NAC in Controls | single intravenous administration of N-acetylcysteine in control subjects |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | NAC in PD | single intravenous administration of N-acetylcysteine in PD patients |
| BG001 | NAC in GD | single intravenous administration of N-acetylcysteine in GD patients |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Brain GSH | change in brain GSH levels from baseline to post-NAC administration (90 - 110 minutes) in all subjects | Posted | Mean | Standard Deviation | percent increase from baseline | Baseline and up to 110 minutes post-NAC administration |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | NAC in PD | single intravenous administration of N-acetylcysteine in PD patients |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| allergic reaction | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Following scan, a subject complained of itchy of hands, nasal congestion, sore throat. Study staff noted swelling around eyes and flushed cheeks & neck. Subject was taken to ER (not admitted)& received standard treatment for allergic reaction to NAC. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mary Holmay | University of Minnesota | 612-812-5854 | holma101@umn.edu |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| D005776 | Gaucher Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D000111 | Acetylcysteine |
| ID | Term |
|---|---|
| D003545 | Cysteine |
| D000603 | Amino Acids, Sulfur |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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| BG002 | NAC in Controls | single intravenous administration of N-acetylcysteine in control subjects |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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single intravenous administration of N-acetylcysteine in control subjects
|
|
| 0 |
| 3 |
| 1 |
| 3 |
| EG001 | NAC in GD | single intravenous administration of N-acetylcysteine in GD patients | 0 | 3 | 0 | 3 |
| EG002 | NAC in Controls | single intravenous administration of N-acetylcysteine in control subjects | 0 | 3 | 0 | 3 |
|
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| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D052439 | Lipid Metabolism Disorders |
| D000596 |
| Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |